Semisynthetic aminoglycosides

Class Semisynthetic aminoglycoside antibiotics with activity against Pseudomonas species, Escherichia coii. Proteus species, Providencia species, Klebsiella species, Enterobacter speaes, Serratia species, Acinetobacter species, Citrobacter freundii, Staphylococcus species Aminoglycosides generally have a low level of activity against grampositive organisms Lo o u c <... 

Netilmicin is a semisynthetic aminoglycoside which is active against some strains of bacteria that resist gentamicin and tobramycin evidence suggests that it may be less oto- and nephrotoxic. 

The spectinomycins (O Fig. 20) have a fused three-ring system which consists of a 4,5-disub-stituted actinamine and an ulose. Spectinomycin is produced by Streptomyces spectabilis and Streptomyces flavopersius. It has been clinically used for treatment of the gonorrhea infection. A related structure has been discovered with spenolimycin which was isolated from the culture filtrate of Streptomyces gilvospiralis. Efforts have been directed toward semisynthetic aminoglycoside antibiotics to treat multi-drug resistant bacteria [94]. 

A semisynthetic aminoglycoside whose design was also based on knowledge of resistance chemistry is the C-l-N-ethylsisomicin, netilimicin. This alkylation protects the drug against ANT (2") and AAC(3)I. 

Amikacin is more potent than kanamycin A and superior to BB-K19 (D,L-HABA) and BB-K31 (D(+)-HABA). Amikacin is the only important semisynthetic aminoglycoside on the market. In this connection two possibilities to synthesise the HABA moiety should be described. One of these syntheses starts with butyrolactone and uses the steps shown in Fig. 46 a. Another method utilizes the 1,3-dipolar addition of the nitrone ester 205 to ethyl acrylate (Fig. 46b). 

Broad-spectrum semisynthetic aminoglycoside related to sisomicin formulated as an injectable. 

C18H36N4O9 452.504 Isol. from Micromonospora inyoensis. Semisynthetic aminoglycoside antibiotic. Sol. H2O poorly sol. Mc2CO, hexane. 

C21H41N5O7 475.584 Semisynthetic aminoglycoside antibiotic. Shows broad spectrum activity. Sol. H2O poorly sol. EtOH, hexane. Mp 100-103°. [a]o +129.5 (H2O). Log P -3.81 (uncertain value) (calc). 

C21H43N5O12 557.597 Semisynthetic aminoglycoside antibiotic. Active against gram-negative bacteria including some aminoglycoside resistant strains. Amorph. Mp 165-170°. 

Netilmicin is a semisynthetic aminoglycoside antibiotic that is active against gram-negative bacteria. Netilmicin is an ethyl derivative (at the 1-N position of the deoxystreptamine ring) of sisomicin. 

The aminoglycoside antibiotic sisomycin has been assayed by reversed-phase h.p.l.c. following pre-column derivatization with Q-phthalaldehyde and 3-mercaptopropionic acid to yield intensely fluorescent 1,2-disubstituted isoindole derivatives. Normally such derivatives are formed post-column because of their instability, but in these studies satisfactory stability was attained. The semisynthetic aminoglycoside netilmicin was... 

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